When specific cells are required for disease treatment, a sufficient amount of cells for achieving treatment goals need to be secured. However, it is difficult to obtain a sufficient amount of cells used for treatment from living organisms. Hence, methods such as a method of preparing target cells by inducing differentiation of their progenitor cells or the like ex vivo are being attempted.
In the case of treating blood-related diseases or performing surgical treatment, blood cells used for the treatment are required. Of blood cells, platelets essential for blood coagulation (hemostasis) and megakaryocytic cells responsible for producing proplatelets and further producing platelets are cells that are especially needed. In particular, platelets are in great demand in treatment of leukemia, bone marrow transplantation, anticancer therapy, and the like, and there is a significant need for stable supply of platelets. Methods used to secure platelets include not only a method of collecting blood from donors, but also a method of administering TPO-mimetic products, a method of differentiating megakaryocytic cells from umbilical cord blood or myeloid cells, and so on. Moreover, methods such as a method of preparing blood cells from hematopoietic stem cells or hematopoietic progenitor cells after amplifying these progenitor cells ex vivo are being attempted. Examples of reported methods include a method of establishing a hematopoietic stem cell line from mouse ES cells (Patent Document 1), a method of differentiating embryonic stem cells of primate animals into hematopoietic cells (Patent Document 2), and a method of easily and stably amplifying CD34-positive/CD38-negative cells that sustain undifferentiation of hematopoietic stem cells ex vivo (Patent Document 3).
When inducing differentiation of cells, pluripotent stem cells are extremely useful. Pluripotent stem cells such as ES cells and iPS cells can be used as a source for artificially producing blood cells such as platelets. In recent years, the establishment of iPS cells has contributed to increasing attention to the usefulness of pluripotent stem cells as an important source for cell therapy in regenerative medicine. For example, Takayama et al. have succeeded in inducing differentiation of human ES cells into megakaryocytic cells and platelets, creating a possibility of using platelets differentiated from ES cells as a source of platelet transfusion (Patent Document 4 and Non-Patent Document 1). The inventors have further established a method of preparing megakaryocytic cells and platelets from iPS cells, making it possible to solve a human leukocyte antigen (HLA) matching problem unavoidable in transfusion of ES cell-derived platelets. Though stable supply of a sufficient amount of platelets through blood donation has conventionally been difficult due to factors such as a chronic shortage of donors, this problem appears to be solvable by differentiation induction of platelets from ES cells or iPS cells. According to the hitherto proposed methods, however, only a small amount of platelets can be prepared from iPS cells or ES cells, and also a series of operations for production needs to be performed each time. It is therefore necessary to provide an improved, efficient method for ensuring quantitative stability of platelets.
Such a problem that needs to be solved in order to stably supply a sufficient amount of blood cells such as megakaryocytic cells and platelets can also be found in supply of other types of cells.
Thus, even in the case of preparing desired cells by differentiation induction of cells, it is still not easy to prepare progenitor cells of desired cells in large amount, so that at present there is difficulty in securing a sufficient amount of terminally-differentiated desired cells.